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Can isoforms of the p53 tumour suppressor cause cancer?

37 months
Approved budget:
Professor Antony Braithwaite
Health issue:
Cancer (oncology)
Proposal type:
Lay summary
p53 is most important for preventing cancer. We know this because mice deleted for the p53 gene are highly tumour prone; in humans, Li-Fraumeni Syndrome, characterized by multiple tumour phenotypes, is due to inherited mutations in p53; and most common human cancers contain p53 mutations. Recently some isoforms of p53 were described. Little is known about their functions, but several are present at elevated levels in human cancers, including melanoma and breast cancer, where p53 is often not mutated. These data, together with recently published in vitro experiments, suggest that one or more p53 isoforms might cause cancer; the opposite of normal p53. We have generated a mouse that expresses the equivalent of the 133p53 isoform of human p53 and have preliminary evidence that it causes cancer. This proposal investigates how it causes cancer. Our results might explain how human cancers form whilst still retaining normal p53 tumour suppressor function.